ArticleJournal of enzyme inhibition and medicinal chemistry2017
Investigation of PDE5/PDE6 and PDE5/PDE11 selective potent tadalafil-like PDE5 inhibitors using combination of molecular modeling approaches, molecular fingerprint-based virtual screening protocols and structure-based pharmacophore development.
Article in Journal of enzyme inhibition and medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- The efficacy and safety of adrenergic alpha-antagonists combined with PDE5 inhibitors in the medical expulsive therapy for unilateral distal ureteral stones: a systematic review and meta-analysis.Translational andrology and urology · 2026Article
- Genetic Association of Sexual Behavior, Sildenafil, and Hormonal Contraceptives With Mental Disorders.CNS neuroscience & therapeutics · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Role of interaction mode of phenanthrene derivatives as selective PDE5 inhibitors using molecular dynamics simulations and quantum chemical calculations.Molecular diversity · 2025Article
- Molecular Dynamics-Assisted Discovery of Novel Phosphodiesterase-5 Inhibitors Targeting a Unique Allosteric Pocket.Molecules (Basel, Switzerland) · 2025Article
- Review
- The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS).Molecular and cellular biochemistry · 2024Review
- Mechanism investigation of highly selective inhibitors toward phosphodiesterase 5 and 6 via theFrontiers in chemistry · 2024Article
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine.Life (Basel, Switzerland) · 2023Article
- Erectile dysfunction and diabetes: A melting pot of circumstances and treatments.Diabetes/metabolism research and reviews · 2022Review
- Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones.Pflugers Archiv : European journal of physiology · 2021Review
- Visual Side Effects Linked to Sildenafil Consumption: An Update.Biomedicines · 2021Review
- The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue.Andrology · 2019Review
- Catalytic Domains of Phosphodiesterase 5, 6, and 5/6 Chimera Display Differential Dynamics and Ligand Dissociation Energy Barriers.The journal of physical chemistry. B · 2019Article
- The phosphodiesterase 5 inhibitor tadalafil regulates lipidic homeostasis in human skeletal muscle cell metabolism.Endocrine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3',5'-cyclic guanosine monophosphate (cGMP) and/or 3',5'-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction. Due to the amino acid sequence and the secondary structural similarity of PDE6 and PDE11 with the catalytic domain of PDE5, first-generation PDE5 inhibitors (i.e. sildenafil and vardenafil) are also competitive inhibitors of PDE6 and PDE11. Since the major challenge of designing novel PDE5 inhibitors is to decrease their cross-reactivity with PDE6 and PDE11, in this study, we attempt to identify potent tadalafil-like PDE5 inhibitors that have PDE5/PDE6 and PDE5/PDE11 selectivity. For this aim, the similarity-based virtual screening protocol is applied for the "clean drug-like subset of ZINC database" that contains more than 20 million small compounds. Moreover, molecular dynamics (MD) simulations of selected hits complexed with PDE5 and off-targets were performed in order to get insights for structural and dynamical behaviors of the selected molecules as selective PDE5 inhibitors. Since tadalafil blocks hERG1 K channels in concentration dependent manner, the cardiotoxicity prediction of the hit molecules was also tested. Results of this study can be useful for designing of novel, safe and selective PDE5 inhibitors.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.